Urothelial bladder cancer (BC) is one of the most prevalent malignancies of the urinary tract, and advanced stages are often associated with poor clinical outcomes. Fibroblast growth factor 5 (FGF5), an oncogenic member of the FGF family, has been implicated in various cancers; however, its role in bladder cancer progression remains poorly understood. FGF5 is believed to promote tumor progression through epithelial–mesenchymal transition (EMT) and inflammation. This study aims to investigate the expression of FGF5 in bladder tumors and explore its functional impact on bladder cancer cells, to evaluate its potential as a therapeutic target.

FGF5 expression levels in human bladder cancer tissues were analyzed using the GEPIA2 database and correlated with patient prognosis. In vitro experiments were conducted using T24 human bladder cancer cells transfected with FGF5-specific siRNA. Cell proliferation was assessed via viability assays, while migration and invasion capabilities were evaluated using wound-healing and Transwell assays. Quantitative PCR and Western blotting were used to analyze the expression of inflammatory cytokines (IL-6, TNF) and EMT markers (E-cadherin/CDH1 and P-cadherin/CDH3). Activation of NF-κB and MAPK signaling pathways was also examined by Western blotting in FGF5-silenced cells compared to controls.

Cancer tissues compared to normal urothelium, and this elevated expression is correlated with poorer patient prognosis. Silencing FGF5 in T24 bladder cancer cells resulted in a marked reduction in cell proliferation, whereas treatment with the FGFR inhibitor Erdafitinib effectively reversed these inhibitory effects, suggesting an FGFR-mediated mechanism. Furthermore, data from the GSE231383 dataset demonstrated high levels of FGF5 expression in T24 cells, which were positively associated with elevated expression of pro-inflammatory cytokines IL-6 and TNF and enhanced epithelial–mesenchymal transition (EMT) features. These findings collectively suggest that the regulated role of FGF5 in bladder cancer is likely mediated through FGFR-dependent inflammatory and EMT-related signaling pathways.

Our findings suggest that FGF5 plays a critical role in promoting bladder cancer progression by enhancing cell proliferation, inflammatory cytokine expression, and EMT, potentially through the activation of NF-κB and MAPK signaling pathways. Given its strong association with poor prognosis and oncogenic features, FGF5 may serve as a promising therapeutic target for the treatment of bladder cancer.